The objective of the proposed research is to gain a better understanding of structural requirements for major histocompatibility complex-dependent antibody recognition of viral antigens on the surfaces of infected cells. Hybridoma antibodies that exhibit haplotype-restricted reactivity with influenza virus hemagglutinin will be used in immunoprecipitation experiments to determine the nature of the antigen that is recognized. The approaches that are proposed will be able to distinguish recognition of a neo-antigenic determinant from reactivity with cross-reactive sites shared by the H-2 on both the virion and the infected cell surface, will be used to select viruses with variant hemagglutinins. These variants will be employed to examine the expression of the individual HA antigenic sites on the infected cell surface and their role in immune recognition. Anti-idiotypic reagents will be raised against monoclonal antibodies to investigate the B-cell clonal diversity of the haplotype-restricted influenza specific response. They will also be used to determine if any correlation exists between idiotype and patterns of reactivity with cells infected with closely-related strains of influenza virus or between idiotype and patterns of recognition of cells from various H-2b mutant mice strains infected with the same strain of influenza. Finally, hybridomas from and an H-2b strain mouse will be produced against uninfected H-2d cells, and used in blocking assays with BALB/C antibodies specific for influenza infected H-2d cells to determine whether the same H-2 sites are involved in allogeneic and "infected self" reactivity.